The roles of prothrombin, thrombin, and antithrombin III in the adhesion of platelets and leukocytes to artificial surfaces will be investigated. Prothrombin and thrombin are important in thrombus generation, while ATIII serves to prevent thrombosis. The kinetics of adsorption of prothrombin, thrombin, and ATIII, singly or in certain combinations under both static and flow conditions will be studied. The interactions of these adsorbed proteins with platelets or leukocytes or other blood components will be examined. A hypothesis that prothrombin may be activated by blood soluble or cellular components following adsorption to artificial surfaces and thus may generate enzymatically active or inactive thrombin that subsequently attracts platelets or leukocytes will be tested. The generation of thrombin from prothrombin will be quantitated by an assay for clotting activity, an assay for esterase activity, and an assay for its reaction with ATIII or with an antithrombin antibody. A radioimmunoassay or an enzyme linked immunosorbent assay will be developed with the antihuman thrombin antibody produced in rabbits to detect and quantitate adsorbed or free thrombin in both enzymatically active and inactive forms. A quantitative relationship between the adsorption of these proteins and platelet or leukocyte adhesion will be delineated in studies with selected, highly purified and well characterized artificial surfaces. Eventually materials obtained from artificial organs such as hemodialyzers, oxygenators or left ventricular assist devices used clinically will be examined. These studies will enhance our knowledge of the mechanisms of interaction of plasma proteins with artificial surfaces, particularly in relation to he adhesion of platelets or leukocytes.